Chapter 14 - Abnormal Social Behaviors and Dysfunction of Autism-Related Genes Associated With Daily Agonistic Interactions in Mice

Abstract

Decline in socialization and communication may be the result of negative social environment, but it can also be due to other environmental as well as genetic factors, leading to the development of affective or neurological disorders, including autistic spectrum disorders. Animal models have been employed to study such disorders. In this chapter, we present a single experimental study as an example. We wish to demonstrate how one can utilize environmental manipulation methods, including social defeat induced stress, to explore behavioral and gene expression changes as a model of abnormal social behavior. In our example, we induced changes in social behaviors by providing repeated experience with social defeat and aggression during daily agonistic interactions in male mice. In addition, we also studied potential alterations in the expression of genes in five brain regions. Analysis of an RNA-Seq database of the whole transcriptome revealed changes in expression of the Tph2, Maoa, Slc6a4, Htr7, Gabrb3, Nrxn1, Nrxn2, Nlgn1, Nlgn2, Nlgn3, Shank2, Shank3, Fmr1, Ube3a, Pten, Cntn3, Foxp2, Oxtr, Reln, Cadps2, Pcdh10, Ctnnd2, En2, Arx, Auts2, Mecp2, and Ptchd1 genes. These genes have also been associated with autism in humans. Our research thus demonstrates for the first time that abnormalities in social behaviors induced by negative social environment in adult mice are associated with altered expression of autism-related genes in the brain. We argue that environmental manipulations may thus represent a potential way the human central nervous system disorders associated with abnormal social behavior could be modeled and analyzed.